The HANDLS study is a prospective, epidemiologic, interdisciplinary, longitudinal study of a baseline representative sample of African Americans and whites between 30-64 years of age recruited as a fixed cohort of participants by household screenings from an area probability sample of twelve census segments in Baltimore City. The HANDLS design is an area probability sample of Baltimore based on the 2000 Census. Using this methodology, working with survey statisticians we chose 12 neighborhoods to meet race by SES by age distribution of the prospective cohort because they were likely to yield representative distributions of Baltimore City with sufficient individuals to fill the sampling design based. Within the 12 neighborhoods, housing units were selected with a known non-zero chance of selection. The addresses were screened for individuals who meet the age-gender-race-poverty sample size, and those were chosen to be included in the sample using a probability sampling method. From these probabilities, we can compute weights to adjust for unequal probabilities of selection. These weights will be needed to compute estimates that combine subjects across any of the age-gender-race-poverty group. The poverty status delimiter is 125% poverty based on 125% of the 2004 Health and Human Services Poverty Guidelines. The initial examination and recruitment phase took approximately 4 years to complete. The study data was collected in two parts. The first part consisted of an in-home interview that included questionnaires about the participants health status, health service utilization, psychosocial factors, nutrition, neighborhood characteristics, and demographics. The second part was collected on the medical research vehicles and included medical history and physical examination, dietary recall, cognitive evaluation, psychophysiology assessments including heart rate variability, arterial thickness, carotid ultrasonography, assessments of muscle strength and bone density, and laboratory measurements (blood chemistries, hematology, biomarkers of oxidative stress and biomaterials for genetic studies). Using our mobile medical research vehicles, we visit each census tract for 4 months and we will re-visit every census tract in a 3.5-year cycle. HANDLS completed its baseline examination wave on March 30, 2009 with a final total accrual of 3720 participants. The cohort is comprised of African American (59%) and Whites (41%). Approximately 41% of the cohort reported a household income below the 125% poverty status delimiter. Of those below the 125% poverty delimiter, 13% were white and 28% African American. Of those above the 125% poverty delimiter, 28% were white and 31% African American. The mean age of the sample was 47.7 years at baseline. There were no significant age differences associated with sex or race. Participants below the 125% poverty delimiter were slightly younger than those above the delimiter. HANDLS medical examination rate was 75.2% comparable to the 75% examination rate for the National Health and Nutrition Examination Study (NHANES). Wave 3 examinations started in July 2009 and was completed in June 2013 with a show rate of 91%. The Wave 3 protocol in keeping with the longitudinal study design maintained many of the same study domains as the baseline wave 1 examination including: cognition, cardiovascular disease, nutrition, physical performance, psychology, health services, genomics (genetics and epigenetics), and molecular biomarkers of disease. This protocol also included new areas of study particularly focused on critical health disparities including, renal function, neuroanatomy, financial and health literacy. These are projects that span a broad range of areas of clinical medicine and include a large number of established minority investigators as well as students and physicians in training. Wave 4 will began September 27 of 2013 and was immediately hampered by the government shut down. The new protocol highlights include an enhanced cardiovascular domain with the addition of the Ankle-Brachial Index, longitudinal assessment of carotid intimal thickness and pulse wave velocity as well as a measure of endothelial dysfunction. Physical activity assessment will also be enhanced by addition of accelerometry and the cognitive domain will use measures that are less dependent on literacy to assess executive function. The Home Visit Protocol developed to prevent the bias resulting from missing data from participants who have become home-bound over the course of the study is ongoing.